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Environmental Epigenetics and Asthma

Current Concepts and Call for Studies

¹ Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, New York; and ² Department of Environmental Health and Cancer Center, College of Medicine, University of Cincinnati, Cincinnati, Ohio

Correspondence and requests for reprints should be addressed to Rachel L. Miller, M.D., PH8E, 630 W. 168th Street, Columbia University College of Physicians and Surgeons, New York, NY 10032. E-mail: rlm14{at}columbia.edu

ABSTRACT

Recent studies suggest that epigenetic regulation (heritable changes in gene expression that occur in the absence of alterations in DNA sequences) may in part mediate the complex gene-by-environment interactions that can lead to asthma. The variable natural history of asthma (i.e., incidence and remission of symptoms) may be a result of epigenetic changes, such as DNA methylation, covalent histone modifications, microRNA changes, and chromatin alterations, after early or later environmental exposures. Findings from multiple epidemiologic and experimental studies indicate that asthma risk may be modified by epigenetic regulation. One study suggested that the transmission of asthma risk may occur across multiple generations. Experimental studies provide substantial in vitro data indicating that DNA methylation of genes critical to T-helper cell differentiation may induce polarization toward or away from an allergic phenotype. Despite this initial progress, fundamental questions remain that need to be addressed by well-designed research studies. Data generated from controlled experiments using in vivo models and/or clinical specimens collected after environmental exposure monitoring are limited. Importantly, cohort-driven epigenetic research has the potential to address key questions, such as those concerning the influence of timing of exposure, dose of exposure, diet, and ethnicity on susceptibility to asthma development. There is immense promise that the study of environmental epigenetics will help us understand a theoretically preventable environmental disease.

Key Words: epigenetics • asthma • DNA methylation • gene–environment interactions